Notice: Undefined index: inline in /home/www/hosts/www.ourexperiment.org/docs/export/xml.php on line 68

Notice: Undefined index: inline in /home/www/hosts/www.ourexperiment.org/docs/export/xml.php on line 68
15871610Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)
Experiments
profiles.google.com-micha.wolfleMichael Wolfle better yield than [url=http://www.ourexperiment.org/racemic_pzq/357]procedure (MW37-1)[/url] but more reagents were used and the preparation required more effort. Used for starting material for: [*] [url=http://www.ourexperiment.org/racemic_pzq/1597]Preparation of the dimethoxybenzyl-N-benzoyl-derivative of the ‘Ugi-intermediate’ (MW52-1)[/url] [*] [url=http://www.ourexperiment.org/racemic_pzq/386]Preparation of the dimethoxy ‘Ugi-intermediate’ via Ugi reaction (MW40)[/url] [b]References:[/b] [url=http://v3.espacenet.com/publicationDetails/biblio?CC=WO&NR=2009115333A1&KC=A1&FT=D&date=20090924&DB=EPODOC&locale=en_ep][1] “Novel Synthesis of Praziquantel“, A. Dömling, [i]Patent Application[/i] [b]2009[/b], WO 2009/11533(A1), Language: German.[/url]]]>Ugi reaction via an alternative route to MW37-1

See also:
  • Preparation of 2-(3,4-dimethoxyphenyl)ethyl isocyanide (MW37-1)
  • Preparation of 2-phenylethyl isocyanide - alternative route (MW34-3)
  • Upscaling - Preparation of 2-Phenylethyl isocyanide (MW34-2)

  • Scheme MW37-2.png


    Hazard and Risk Assessment:
    HRAF MW37-2.pdf


    Start time: 4:00 PM 10/02/2011
    End time: 3:00 PM 11/02/2011

    Problems to access the website from 11/02/2011 to 14/02/2011

    A solution of 3,4-dimethoxyphenethylamine (2.00 g, 11.0 mmol, M.W. 181.2 g/mol) was heated to reflux in ethyl formate (10 mL, M.W. 74.1 g/mol, bp 52-54°C) and heated to reflux for 18 h.
    The remaining ethyl formiate and the by-product ethanol were removed under reduced pressure obtaining a yellow liquid.
    2-(3,4-Dimethoxyphenyl)ethylformamide and triethylamine (3.35 g, 33.1 mmol, 4.62 mL, 3.0 eq., M.W. 101.2, d=0.726 g/mL) were dissoved in dry DCM (20 mL) and phosphoryl chloride (1.69 g, 11.0 mmol, 1.03 mL, 1.0 eq., M.W. 153.3, d=1.645 g/mL) was dropwise added at 0°C. The mixture was stirred for 1 h at 0°C and a further 4 h at room temperature.
    The mixture was quenched with water and neutralized with NaHCO3 solution. The organic layer was seperated and the aqueous solution was extracted 3 times with DCM. The combined organic layers were dried over magnesium sulfate and evaporated afforded a dark brown oil.

    - purification by column chromatography (silica gel, hexane/EA, 3:1, stain: KMnO4, Rf = 0.25)

    Yield: 1.39 g (7.27 mmol, 66%) orange liquid
    [M.W. = 191.2 g/mol]

    1H NMR: (CDCl3, 200 MHz): δ = 2.92 (t, J=6.9 Hz, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.86 (s, 3H), 3.88 (s, 3H), 6.75-6.86 (m, 3 H).
    Data: 1H NMR MW37-2.pdf

    -> better yield than procedure (MW37-1) but more reagents were used and the preparation required more effort.

    Used for starting material for:
  • Preparation of the dimethoxybenzyl-N-benzoyl-derivative of the ‘Ugi-intermediate’ (MW52-1)
  • Preparation of the dimethoxy ‘Ugi-intermediate’ via Ugi reaction (MW40)

    References:
  • [1] “Novel Synthesis of Praziquantel“, A. Dömling, Patent Application 2009, WO 2009/11533(A1), Language: German.
    ]]>2011-02-10T04:36:25+00:002011-02-15T05:02:21+00:006cbcbb94ce684bd252a8d5dcdb2f2cd94https://www.ourexperiment.org/data/785.xmlhttps://www.ourexperiment.org/data/787.xmlhttps://www.ourexperiment.org/data/793.xmlhttps://www.ourexperiment.org/data/795.xmlhttp://www.ourexperiment.org/uri/104https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.htmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.htmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.pnghttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1587https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1588https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1589https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1590https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1595https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1596https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1603https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1606https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1607https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1610https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=718231Re: Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)ErrorRe: Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)Nice. I hope this works smoothly. This is the likeliest route to a benzoyl analog of PZQ via the P-S I think.Nice. I hope this works smoothly. This is the likeliest route to a benzoyl analog of PZQ via the P-S I think.2011-02-10T11:24:33+00:00
    15877182Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)
    Experiments
    profiles.google.com-micha.wolfleMichael Wolfle better yield than [url=http://www.ourexperiment.org/racemic_pzq/357]procedure (MW37-1)[/url] but more reagents were used and the preparation required more effort. Used for starting material for: [*] [url=http://www.ourexperiment.org/racemic_pzq/1597]Preparation of the dimethoxybenzyl-N-benzoyl-derivative of the ‘Ugi-intermediate’ (MW52-1)[/url] [*] [url=http://www.ourexperiment.org/racemic_pzq/386]Preparation of the dimethoxy ‘Ugi-intermediate’ via Ugi reaction (MW40)[/url] [b]References:[/b] [url=http://v3.espacenet.com/publicationDetails/biblio?CC=WO&NR=2009115333A1&KC=A1&FT=D&date=20090924&DB=EPODOC&locale=en_ep][1] “Novel Synthesis of Praziquantel“, A. Dömling, [i]Patent Application[/i] [b]2009[/b], WO 2009/11533(A1), Language: German.[/url]]]>Ugi reaction via an alternative route to MW37-1

    See also:
  • Preparation of 2-(3,4-dimethoxyphenyl)ethyl isocyanide (MW37-1)
  • Preparation of 2-phenylethyl isocyanide - alternative route (MW34-3)
  • Upscaling - Preparation of 2-Phenylethyl isocyanide (MW34-2)

  • Scheme MW37-2.png


    Hazard and Risk Assessment:
    HRAF MW37-2.pdf


    Start time: 4:00 PM 10/02/2011
    End time: 3:00 PM 11/02/2011

    Problems to access the website from 11/02/2011 to 14/02/2011

    A solution of 3,4-dimethoxyphenethylamine (2.00 g, 11.0 mmol, M.W. 181.2 g/mol) was heated to reflux in ethyl formate (10 mL, M.W. 74.1 g/mol, bp 52-54°C) and heated to reflux for 18 h.
    The remaining ethyl formiate and the by-product ethanol were removed under reduced pressure obtaining a yellow liquid.
    2-(3,4-Dimethoxyphenyl)ethylformamide and triethylamine (3.35 g, 33.1 mmol, 4.62 mL, 3.0 eq., M.W. 101.2, d=0.726 g/mL) were dissoved in dry DCM (20 mL) and phosphoryl chloride (1.69 g, 11.0 mmol, 1.03 mL, 1.0 eq., M.W. 153.3, d=1.645 g/mL) was dropwise added at 0°C. The mixture was stirred for 1 h at 0°C and a further 4 h at room temperature.
    The mixture was quenched with water and neutralized with NaHCO3 solution. The organic layer was seperated and the aqueous solution was extracted 3 times with DCM. The combined organic layers were dried over magnesium sulfate and evaporated afforded a dark brown oil.

    - purification by column chromatography (silica gel, hexane/EA, 3:1, stain: KMnO4, Rf = 0.25)

    Yield: 1.39 g (7.27 mmol, 66%) orange liquid
    [M.W. = 191.2 g/mol]

    1H NMR: (CDCl3, 200 MHz): δ = 2.92 (t, J=6.9 Hz, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.86 (s, 3H), 3.88 (s, 3H), 6.75-6.86 (m, 3 H).
    Data: 1H NMR MW37-2.pdf

    -> better yield than procedure (MW37-1) but more reagents were used and the preparation required more effort.

    Used for starting material for:
  • Preparation of the dimethoxybenzyl-N-benzoyl-derivative of the ‘Ugi-intermediate’ (MW52-1)
  • Preparation of the dimethoxy ‘Ugi-intermediate’ via Ugi reaction (MW40)

    References:
  • [1] “Novel Synthesis of Praziquantel“, A. Dömling, Patent Application 2009, WO 2009/11533(A1), Language: German.
    ]]>2011-02-10T04:36:25+00:002015-07-19T23:02:42+01:006https://www.ourexperiment.org/data/785.xmlhttps://www.ourexperiment.org/data/787.xmlhttps://www.ourexperiment.org/data/793.xmlhttps://www.ourexperiment.org/data/795.xmlhttp://www.ourexperiment.org/uri/104https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.htmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.htmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xmlhttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.pnghttps://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1587https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1588https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1589https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1590https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1595https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1596https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1603https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1606https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1607https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=1610https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=7182https://www.ourexperiment.org/racemic_pzq/1587/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW372.xml?revision=-131Re: Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)ErrorRe: Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)Nice. I hope this works smoothly. This is the likeliest route to a benzoyl analog of PZQ via the P-S I think.Nice. I hope this works smoothly. This is the likeliest route to a benzoyl analog of PZQ via the P-S I think.2011-02-10T11:24:33+00:00